The renin-angiotensin-aldosterone systems and renal kallikrein and prostaglandins normally participate in the homeostatic regulation of electrolyte and acid-base composition, extracellular fluid volume and blood pressure. We are studying abnormalities of these hormonal systems in disorders of electrolyte and acid-base metabolims and hypertension in human beings. Aldosterone deficiency, usually occurring as a consequence of a primary deficiency of renin secretion (hyporenineumic hypoaldosteronism), is a common finding in patients with chronic renal insufficiency and an important cause of significant hyperkalemia and hyperchloremic metabolic acidosis. Studies under metabolic ward conditions with rigorous control of net potassium load and administration of pharmacologic agents (captopril, indomethasin) are utilized to define the relationship between the hormonal systems and maintenance of potassium and acid-base homeostasis. Studies of these hormonal systems are being conducted in patients with various hypokalemic syndromes due to renal potassium wasting and in normal subjects made hypokalemic by dietary potassium restriction. The effect of hypokalemia on solute transport in the diluting segment of the nephron and the effect of treatment with a "potassium sparing" agent, amiloride, are also being evaluated in this study population. Studies ae being conducted in hypertensive disorders characterized by increased activity of the renin-angiotensin systems and/or adrenal mineralocorticoid hormones to define the pathogenic adnormalities and to determine optimal therapy for such patients. The relationship between extracellular fluid volume and the renal kallikrein and protaglandin systems in the pathogenesis of hypertension in patients with chronic renal insufficiency is also under investigation.